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Article

Ginkgo biloba extract enhances chemotherapy sensitivity and reverses chemoresistance through suppression of the KSR1-mediated ERK1/2 pathway in gastric cancer cells

  • Authors:
    • Shi-Quan Liu
    • Chun-Yan Xu
    • Meng-Bin Qin
    • Lin Tan
    • Chun-Feng Zhuge
    • Ye-Bo Mao
    • Ming-Yu Lai
    • Jie-An Huang
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
  • Pages: 2871-2882
    |
    Published online on: April 24, 2015
       https://doi.org/10.3892/or.2015.3923
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Abstract

Kinase suppressor of Ras 1 (KSR1) is a scaffold protein that modulates the activation of the oncogenic mitogen‑activated protein kinase (MAPK)/extracellular signal‑regulated kinase (ERK) signaling pathway. Ginkgo biloba extract (EGb) 761 has been demonstrated to possess antitumor activity that may be related to the KSR1‑mediated ERK signaling pathway. However, the roles and its underlying mechanism in gastric cancer are unclear. In the present study, 62 gastric cancer and matched normal tissues were exploited for immunohistochemistry and real‑time fluorescent quantitative PCR detection. Results of the immunohistochemistry showed that the expression of ERK1/2 and p-ERK1/2 was correlated to the expression of KSR1 and p-KSR1 in the gastric cancer tissues, and the overexpression of KSR1, p-KSR1, ERK1/2 and p-ERK1/2 was significantly associated with histological grade, TNM stage, lymph node and distant metastasis. Compared with the normal tissues, the relative mRNA copy values of KSR1, ERK1 and ERK2 in the cancer tissues were 2.43±0.49, 2.10±0.44 and 3.65±0.94. In addition, the expression of KSR1, p-KSR1, ERK1/2 and p-ERK1/2 in human gastric cancer multidrug resistant SGC-7901/CDDP cells was higher than that in the SGC-7901 cells as detected by the methods of immunocytochemistry and western blot analysis. EGb 761 not only suppressed expression of these proteins induced by cisplatin (CDDP) and etoposide in SGC-7901 cells, but also inhibited expression of these proteins in the SGC-7901/CDDP cells. Meanwhile, the proliferation‑suppressing and apoptosis‑inducing capacities of CDDP and etoposide were enhanced following combined treatment with EGb 761. Moreover, EGb 761 reduced the malondialdehyde (MDA) content and elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the tumor cells. These results confirmed that activation of the KSR1-mediated ERK1/2 signaling pathway may contribute to tumorigenesis, metastasis and chemoresistance of human gastric cancer. EGb 761 enhanced the chemotherapy sensitivity and reversed the chemoresistance through suppression of the KSR1-mediated ERK1/2 pathway in gastric cancer cells, and the underlying mechanism may be related to its antioxidative activity.
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Copy and paste a formatted citation
Spandidos Publications style
Liu S, Xu C, Qin M, Tan L, Zhuge C, Mao Y, Lai M and Huang J: Ginkgo biloba extract enhances chemotherapy sensitivity and reverses chemoresistance through suppression of the KSR1-mediated ERK1/2 pathway in gastric cancer cells. Oncol Rep 33: 2871-2882, 2015.
APA
Liu, S., Xu, C., Qin, M., Tan, L., Zhuge, C., Mao, Y. ... Huang, J. (2015). Ginkgo biloba extract enhances chemotherapy sensitivity and reverses chemoresistance through suppression of the KSR1-mediated ERK1/2 pathway in gastric cancer cells. Oncology Reports, 33, 2871-2882. https://doi.org/10.3892/or.2015.3923
MLA
Liu, S., Xu, C., Qin, M., Tan, L., Zhuge, C., Mao, Y., Lai, M., Huang, J."Ginkgo biloba extract enhances chemotherapy sensitivity and reverses chemoresistance through suppression of the KSR1-mediated ERK1/2 pathway in gastric cancer cells". Oncology Reports 33.6 (2015): 2871-2882.
Chicago
Liu, S., Xu, C., Qin, M., Tan, L., Zhuge, C., Mao, Y., Lai, M., Huang, J."Ginkgo biloba extract enhances chemotherapy sensitivity and reverses chemoresistance through suppression of the KSR1-mediated ERK1/2 pathway in gastric cancer cells". Oncology Reports 33, no. 6 (2015): 2871-2882. https://doi.org/10.3892/or.2015.3923
Copy and paste a formatted citation
x
Spandidos Publications style
Liu S, Xu C, Qin M, Tan L, Zhuge C, Mao Y, Lai M and Huang J: Ginkgo biloba extract enhances chemotherapy sensitivity and reverses chemoresistance through suppression of the KSR1-mediated ERK1/2 pathway in gastric cancer cells. Oncol Rep 33: 2871-2882, 2015.
APA
Liu, S., Xu, C., Qin, M., Tan, L., Zhuge, C., Mao, Y. ... Huang, J. (2015). Ginkgo biloba extract enhances chemotherapy sensitivity and reverses chemoresistance through suppression of the KSR1-mediated ERK1/2 pathway in gastric cancer cells. Oncology Reports, 33, 2871-2882. https://doi.org/10.3892/or.2015.3923
MLA
Liu, S., Xu, C., Qin, M., Tan, L., Zhuge, C., Mao, Y., Lai, M., Huang, J."Ginkgo biloba extract enhances chemotherapy sensitivity and reverses chemoresistance through suppression of the KSR1-mediated ERK1/2 pathway in gastric cancer cells". Oncology Reports 33.6 (2015): 2871-2882.
Chicago
Liu, S., Xu, C., Qin, M., Tan, L., Zhuge, C., Mao, Y., Lai, M., Huang, J."Ginkgo biloba extract enhances chemotherapy sensitivity and reverses chemoresistance through suppression of the KSR1-mediated ERK1/2 pathway in gastric cancer cells". Oncology Reports 33, no. 6 (2015): 2871-2882. https://doi.org/10.3892/or.2015.3923
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